This revised renewal proposal is to investigate the mechanisms by which certain interventions protect against the cascade of deleterious events that follow a period of spinal ischemia. There are two specific aims. The first is to define the optimal thermal and temporal characteristics of perischemic cooling. Measures of ischemic consequences or correlative changes with protection include spinal extracellular potassium, dorsal horn neuronal activity, amino acid and PGE2 release, neurological outcome at 2-5 days and spinal histopathology. The second aim is to define the factors governing spinal expression of HSP72 and immediate early genes, and the correlation of such expression with post-ischemia functional recovery. hsp72, c-fos and c-jun expression will be measured following transient cooling or heating to two different temperatures, intrathecal delivery of substance P; NMDA, AMPA, or kainic acid; high potassium; or either of two transient non-injurious intervals of spinal ischemia. The protective effects of these manipulations will be measured on damage observed with a fixed injurious duration of ischemia delivered at 3 different intervals after the conditioning treatments which induce hsp72 and/or fos/jun expression; measures of damage include neurologic outcome, spinal amino acid and PGE2 release and histopathology. The role of HSP72 expression in protection will be tested by examining the effects of antisense pretreatment on HSP72 expression and the same three measures of ischemic damage.